Cannabis is widely used by cancer patients, and has many real benefits for those going through cancer and chemotherapy. As we have written on quite extensively, cannabis can help treat pain, inflammation, decrease nausea, increase hunger, and improve sleep quality. These are all vital for the wellbeing and survival of cancer patients, and their efficacy is widely accepted for those uses. But, cancer treatments are rapidly changing, and chemotherapy is being used less today than in the past, primarily due to the rise of new immunotherapies. Immunotherapies come in many forms, such as drugs or genetic modification as in CAR-T therapy, but the general idea is that the body’s own immune system is used to beat the cancer rather than radiation or a cocktail of chemicals.
These new therapies are showing great potential, and are being hailed as the fourth pillar of cancer treatment (after surgery, radiation, and chemotherapy), however success is still relatively low for many cohorts and cancer types. Most scientists in that field believe that is just a matter of reaching the potential that is there, which can take time. However, researchers out of Israel have just published a study that should give reason for concern to any cancer patients being treated with immunotherapies and also using cannabis regularly.
The study design
The study that may be a cause for concern was published on August 28, 2020 in the Journal Cancers, under the title “Cannabis Consumption Used by Cancer Patients during Immunotherapy Correlates with Poor Clinical Outcome.” The study looked at a small group of 102 patients that had advanced stage cancers with tumors (not all cancers have tumors, like blood cancers) and were enrolled in an immunotherapy treatment program. More than 50% of the patients being treated had been diagnosed with non-small cell lung cancers. Of those 102, 68 were only receiving the immunotherapy, and 34 were receiving immunotherapy plus cannabis (non-users vs users, respectively).
Prior to beginning treatment, all participants were given a novel blood test that checked for endogenous endocannabinoids (ECBs) and ECB-like lipid levels in the blood serum. These are the compounds that are found in the body’s endocannabinoid system which, among other things, play a major role in modulating the immune system. These ECBs also trigger the same receptors as the phytocannabinoids (i.e. THC, CBD, CBN, etc.) found in the Cannabis sativa plant. At this stage, there was very little difference in the abundance of most ECBs between the user and non-user groups within the blood serum. However, there was a significant difference in the abundance of leukocytes (a type of white blood cell), with 16% more of the user groups having a low level (67% of cannabis users vs. 51% of non-users). Next, the patients were started on immunotherapy, and evaluated for ECB levels, complications, disease/tumor progression, and death. There were mixed results between those categories.
The Study Results
Of all the various ECB levels tested from blood serum, 9 showed significant differences between the two cohorts after immunotherapy. However, since very little is currently known how these ECBs work together to modulate the immune system, it is hard to determine whether any of those should be viewed as positive or negative in the treatment of cancer. The body’s endocannabinoid system was only discovered in the past 30 years, and this study had to create a novel process in order to assess the level of ECBs, but still little is known about what those levels mean, or if the circulating levels represent the levels at the receptors. We do know the properties of each compound, but what is still unknown is how they work in unison, in what the authors termed the “endocannabinoidome, (similar to the word microbiome to describe the complex communities of microorganisms in our gut).
The next factor assessed was complications to treatment. In this case, they usually arise as the bodies immune system attacking healthy cells after being supercharged by the treatment. In this study, this materialized in the form of problems with the skin, GI tract, or thyroid. The interesting finding however was that the user group had a much lower incidence of adverse immune response, with 39% in the non-user group and only 21% in the cannabis user group. This finding implies that the cannabis down-regulated the immune response, and prevented the body’s immune system from attacking its host. This was one positive finding for the cannabis cohort, but would it lead to better overall survival?
When it came to treatment outcome, three classes of successful treatment were established, those with complete response (no disease), partial response (some improvement), and stable disease (no further progression). In this case, the cannabis cohort fell short, with only 39% reaching one of those states, compared with 51% of the non-users. In the end, cannabis users were more likely to show signs of disease progression following immunotherapy treatment than those who did not use cannabis.
The last factor assessed was the time to relapse (tumor progression) or death, which again showed marked decreases in the cannabis using cohort. For the user group, the time to tumor progression was an average of just 3.2 months, compared with 28.5 months for the non-users. Users also suffered earlier mortality, with a 2.18 hazard ratio compared with non-users (they were about twice as likely to die during the study period.) these results are quite alarming for many cancer patients who have found great relief from cannabis to treat their disease and its symptoms, but are they the end of the story?
Limitations to this study
This study had many limitations that were identified by the authors, such as the small sample size, the variability in cannabis usage, the differences in diagnosis, differences in comorbidities, and other research limits. However, what they failed to point out explicitly was that the cannabis user cohort was generally on the second line of treatment (76%) while only half of the non-user cohort were on their second line of treatment (54%). This data was included in a table in the publication, but not brought up in the text, and, this author would argue, plays an extremely significant role in the outcomes of the patients. I can tell you from experience that first treatments bring a lot of optimism, that in turn brings them a lot of success. This can be put down to many factors, such as the placebo effect, the effects that positive mental state has on the somatic nervous system, and the fact that the body has not yet been subjected to harsh protocols such as radiation or chemo. Secondary treatment options only come when the first line of treatment fails, and often these secondary treatments have a veil of desperation, despair, and negativity hanging over them. Because of how important a positive attitude and the drive to get better is a proxy for survival, second line treatments generally have poorer outcomes.
So, it is very interesting that the authors covered so many of the limitations of this study, but neglected to even discuss in passing the effects that a second line treatment would have compared to immunotherapy as the first treatment. It could be because they are not cancer survivors themselves, and have not experienced this. But that is unlikely because they are working with cancer patients every day, and are well aware of the existing literature. More likely, it was that they wanted their results to appear more significant than they actually were.
So, is cannabis dangerous to cancer patients?
If patients are receiving traditional cancer therapies than the risks of complications due to the cannabis are low, and generally are associated with smoking raw flower (fungal infections, chronic bronchitis, pneumonia, secondary cancers, etc.) And for most patients, the benefits in areas such as pain, inflammation, sleep, and hunger outweigh any negative issues such as drowsiness or intoxication. But, it is important to realize that these new therapeutics that act on the immune system are also acting upon the endocannabinoid system, and the phytocannabinoids in the cannabis plant will alter the effects of that treatment in ways that we are yet to understand. Although this study is not conclusive in any way, it does make a good case for further investigations, and also gives good reason for caution. If you are a cancer patient and are thinking of trying immunotherapy you should make sure your doctor is aware of your cannabis use, and you should be aware that, at least in preliminary studies, cannabis use was associated with increased disease progressions and decreased survival.